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Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform proto...

Gerhardt Attard, Laura Murphy, Noel W Clarke, Ashwin Sachdeva, Craig Jones, Alex Hoyle, William Cross, Robert J Jones, Christopher C Parker, Silke Gillessen, Adrian Cook, Chris Brawley, Clare Gilson, Hannah Rush, Hoda Abdel-Aty, Claire L Amos, Claire Murphy, Simon Chowdhury, Zafar Malik, J Martin Russell, Nazia Parkar, Cheryl Pugh, Carlos Diaz-Montana, Carmel Pezaro, Warren Grant, Helen Saxby, Ian Pedley, Joe M O'Sullivan, Alison Birtle, Joanna Gale, Narayanan Srihari, Carys Thomas, Jacob Tanguay, John Wagstaff, Prantik Das, Emma Gray, Mymoona Alzouebi, Omi Parikh, Angus Robinson, Amir H Montazeri, James Wylie, Anjali Zarkar, Richard Cathomas, Michael D Brown, Yatin Jain, David P Dearnaley, Malcolm D Mason, Duncan Gilbert, Ruth E Langley, Robin Millman, David Matheson, Matthew R Sydes, Louise C Brown, Mahesh K B Parmar, Nicholas D James, Elin Jones, Katherine Hyde, Hilary Glen, Sarah Needleman, Ursula McGovern, Denise Sheehan, Sangeeta Paisey, Richard Shaffer, Mark Beresford, Zafar Malik, Anjali Zarkar, Emilio Porfiri, David Fackrell, Ling Lee, Thiagarajan Sreenivasan, Sue Brock, Simon Brown, Amit Bahl, Mike Smith-Howell, Cathryn Woodward, Mau-Don Phan, Danish Mazhar, Krishna Narahari, Jacob Tanguay, Fiona Douglas, Anil Kumar, Abdel Hamid, Azman Ibrahim, Dakshinamoorthy Muthukumar, Matthew Simms, Jane Worlding, Anna Tran, Mohammed Kagzi, Prantik Das, Carmel Pezaro, Virgil Sivoglo, Benjamin Masters, Pek Keng-Koh, Caroline Manetta, Duncan McLaren, Nishi Gupta, Denise Sheehan, Stergios Boussios, Henry Taylor, John Graham, Carla Perna, Lucinda Melcher, Warren Grant, Katherine Hyde, Ami Sabharwal, Uschi Hofmann, Robert Dealey, Neil McPhail, Robert Brierly, Simon Brown, Lisa Capaldi, Norma Sidek, Peter Whelan, Thiagarajan Sreenivasan, Peter Robson, Alison Falconer, Sarah Rudman, Sindu Vivekanandan, Vinod Mullessey, Sarah Needleman, Maria Vilarino-Varela, Vincent Khoo, Karen Tipples, Mehran Afshar, Alison Falconer, Patryk Brulinski, Vijay Sangar, Clive Peedell, Ashraf Azzabi, Peter Hoskin, Viwod Mullassery, Santhanam Sundar, Yakhub Khan, Ruth Conroy, Andrew Protheroe, Judith Carser, Paul Rogers, Lisa Capaldi, Kathryn Tarver, Stephanie Gibbs, Mohammad Muneeb Khan, Mohan Hingorani, Ashraf Azzabi, Simon Crabb, Manal Alameddine, Neeraj Bhalla, Caroline Manetta, Robert Hughes, John Logue, Darren Leaning, Salil Vengalil, Ashraf Azzabi, Daniel Ford, Georgina Walker, Ahmed Shaheen, Omar Khan, Andrew Chan, Imtiaz Ahmed, Serena Hilman, Fiona Douglas, Anil Kumar, Anna Tran, Sangeeta Paisey, Ian Sayers, Lisa Capaldi, Ashok Nikapota, David Bloomfield, Tim Porter, Joji Joseph, Cyrill Rentsch, Ricardo Pereira Mestre, Enrico Roggero, Jörg Beyer, Markus Borner, Raeto Strebel, Dominik Berthold, Daniel Engeler, Hubert John, Razvan Popescu, Donat Durr, John Wagstaff

The Lancet Oncology, Volume: 24, Issue: 5, Pages: 443 - 456

Swansea University Author: John Wagstaff

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DOI (Published version): 10.1016/s1470-2045(23)00148-1

Abstract

BackgroundAbiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide...

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Published in: The Lancet Oncology
ISSN: 1470-2045
Published: Elsevier BV 2023
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa66427
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fullrecord <?xml version="1.0" encoding="utf-8"?><rfc1807 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xsd="http://www.w3.org/2001/XMLSchema"><bib-version>v2</bib-version><id>66427</id><entry>2024-05-15</entry><title>Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol</title><swanseaauthors><author><sid>fdab5e9e2fe06c93d3ffa19c816bdcf6</sid><firstname>John</firstname><surname>Wagstaff</surname><name>John Wagstaff</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2024-05-15</date><deptcode>MEDS</deptcode><abstract>BackgroundAbiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.MethodsWe analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).FindingsBetween Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p&lt;0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p&lt;0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (&lt;1%) with standard of care in the abiraterone trial).InterpretationEnzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.</abstract><type>Journal Article</type><journal>The Lancet Oncology</journal><volume>24</volume><journalNumber>5</journalNumber><paginationStart>443</paginationStart><paginationEnd>456</paginationEnd><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>1470-2045</issnPrint><issnElectronic/><keywords/><publishedDay>2</publishedDay><publishedMonth>5</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-05-02</publishedDate><doi>10.1016/s1470-2045(23)00148-1</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.</funders><projectreference/><lastEdited>2024-06-19T15:22:56.7465510</lastEdited><Created>2024-05-15T08:58:13.7814657</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Gerhardt</firstname><surname>Attard</surname><order>1</order></author><author><firstname>Laura</firstname><surname>Murphy</surname><order>2</order></author><author><firstname>Noel W</firstname><surname>Clarke</surname><order>3</order></author><author><firstname>Ashwin</firstname><surname>Sachdeva</surname><order>4</order></author><author><firstname>Craig</firstname><surname>Jones</surname><order>5</order></author><author><firstname>Alex</firstname><surname>Hoyle</surname><order>6</order></author><author><firstname>William</firstname><surname>Cross</surname><order>7</order></author><author><firstname>Robert J</firstname><surname>Jones</surname><order>8</order></author><author><firstname>Christopher C</firstname><surname>Parker</surname><order>9</order></author><author><firstname>Silke</firstname><surname>Gillessen</surname><order>10</order></author><author><firstname>Adrian</firstname><surname>Cook</surname><order>11</order></author><author><firstname>Chris</firstname><surname>Brawley</surname><order>12</order></author><author><firstname>Clare</firstname><surname>Gilson</surname><order>13</order></author><author><firstname>Hannah</firstname><surname>Rush</surname><order>14</order></author><author><firstname>Hoda</firstname><surname>Abdel-Aty</surname><order>15</order></author><author><firstname>Claire L</firstname><surname>Amos</surname><order>16</order></author><author><firstname>Claire</firstname><surname>Murphy</surname><order>17</order></author><author><firstname>Simon</firstname><surname>Chowdhury</surname><order>18</order></author><author><firstname>Zafar</firstname><surname>Malik</surname><order>19</order></author><author><firstname>J Martin</firstname><surname>Russell</surname><order>20</order></author><author><firstname>Nazia</firstname><surname>Parkar</surname><order>21</order></author><author><firstname>Cheryl</firstname><surname>Pugh</surname><order>22</order></author><author><firstname>Carlos</firstname><surname>Diaz-Montana</surname><order>23</order></author><author><firstname>Carmel</firstname><surname>Pezaro</surname><order>24</order></author><author><firstname>Warren</firstname><surname>Grant</surname><order>25</order></author><author><firstname>Helen</firstname><surname>Saxby</surname><order>26</order></author><author><firstname>Ian</firstname><surname>Pedley</surname><order>27</order></author><author><firstname>Joe M</firstname><surname>O'Sullivan</surname><order>28</order></author><author><firstname>Alison</firstname><surname>Birtle</surname><order>29</order></author><author><firstname>Joanna</firstname><surname>Gale</surname><order>30</order></author><author><firstname>Narayanan</firstname><surname>Srihari</surname><order>31</order></author><author><firstname>Carys</firstname><surname>Thomas</surname><order>32</order></author><author><firstname>Jacob</firstname><surname>Tanguay</surname><order>33</order></author><author><firstname>John</firstname><surname>Wagstaff</surname><order>34</order></author><author><firstname>Prantik</firstname><surname>Das</surname><order>35</order></author><author><firstname>Emma</firstname><surname>Gray</surname><order>36</order></author><author><firstname>Mymoona</firstname><surname>Alzouebi</surname><order>37</order></author><author><firstname>Omi</firstname><surname>Parikh</surname><order>38</order></author><author><firstname>Angus</firstname><surname>Robinson</surname><order>39</order></author><author><firstname>Amir 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111</order></author><author><firstname>Norma</firstname><surname>Sidek</surname><order>112</order></author><author><firstname>Peter</firstname><surname>Whelan</surname><order>113</order></author><author><firstname>Thiagarajan</firstname><surname>Sreenivasan</surname><order>114</order></author><author><firstname>Peter</firstname><surname>Robson</surname><order>115</order></author><author><firstname>Alison</firstname><surname>Falconer</surname><order>116</order></author><author><firstname>Sarah</firstname><surname>Rudman</surname><order>117</order></author><author><firstname>Sindu</firstname><surname>Vivekanandan</surname><order>118</order></author><author><firstname>Vinod</firstname><surname>Mullessey</surname><order>119</order></author><author><firstname>Sarah</firstname><surname>Needleman</surname><order>120</order></author><author><firstname>Maria</firstname><surname>Vilarino-Varela</surname><order>121</order></author><author><firstname>Vincent</firstname><surname>Khoo</surname><order>122</order></author><author><firstname>Karen</firstname><surname>Tipples</surname><order>123</order></author><author><firstname>Mehran</firstname><surname>Afshar</surname><order>124</order></author><author><firstname>Alison</firstname><surname>Falconer</surname><order>125</order></author><author><firstname>Patryk</firstname><surname>Brulinski</surname><order>126</order></author><author><firstname>Vijay</firstname><surname>Sangar</surname><order>127</order></author><author><firstname>Clive</firstname><surname>Peedell</surname><order>128</order></author><author><firstname>Ashraf</firstname><surname>Azzabi</surname><order>129</order></author><author><firstname>Peter</firstname><surname>Hoskin</surname><order>130</order></author><author><firstname>Viwod</firstname><surname>Mullassery</surname><order>131</order></author><author><firstname>Santhanam</firstname><surname>Sundar</surname><order>132</order></author><author><firstname>Yakhub</firstname><surname>Khan</surname><order>133</order></author><author><firstname>Ruth</firstname><surname>Conroy</surname><order>134</order></author><author><firstname>Andrew</firstname><surname>Protheroe</surname><order>135</order></author><author><firstname>Judith</firstname><surname>Carser</surname><order>136</order></author><author><firstname>Paul</firstname><surname>Rogers</surname><order>137</order></author><author><firstname>Lisa</firstname><surname>Capaldi</surname><order>138</order></author><author><firstname>Kathryn</firstname><surname>Tarver</surname><order>139</order></author><author><firstname>Stephanie</firstname><surname>Gibbs</surname><order>140</order></author><author><firstname>Mohammad Muneeb</firstname><surname>Khan</surname><order>141</order></author><author><firstname>Mohan</firstname><surname>Hingorani</surname><order>142</order></author><author><firstname>Ashraf</firstname><surname>Azzabi</surname><order>143</order></author><author><firstname>Simon</firstname><surname>Crabb</surname><order>144</order></author><author><firstname>Manal</firstname><surname>Alameddine</surname><order>145</order></author><author><firstname>Neeraj</firstname><surname>Bhalla</surname><order>146</order></author><author><firstname>Caroline</firstname><surname>Manetta</surname><order>147</order></author><author><firstname>Robert</firstname><surname>Hughes</surname><order>148</order></author><author><firstname>John</firstname><surname>Logue</surname><order>149</order></author><author><firstname>Darren</firstname><surname>Leaning</surname><order>150</order></author><author><firstname>Salil</firstname><surname>Vengalil</surname><order>151</order></author><author><firstname>Ashraf</firstname><surname>Azzabi</surname><order>152</order></author><author><firstname>Daniel</firstname><surname>Ford</surname><order>153</order></author><author><firstname>Georgina</firstname><surname>Walker</surname><order>154</order></author><author><firstname>Ahmed</firstname><surname>Shaheen</surname><order>155</order></author><author><firstname>Omar</firstname><surname>Khan</surname><order>156</order></author><author><firstname>Andrew</firstname><surname>Chan</surname><order>157</order></author><author><firstname>Imtiaz</firstname><surname>Ahmed</surname><order>158</order></author><author><firstname>Serena</firstname><surname>Hilman</surname><order>159</order></author><author><firstname>Fiona</firstname><surname>Douglas</surname><order>160</order></author><author><firstname>Anil</firstname><surname>Kumar</surname><order>161</order></author><author><firstname>Anna</firstname><surname>Tran</surname><order>162</order></author><author><firstname>Sangeeta</firstname><surname>Paisey</surname><order>163</order></author><author><firstname>Ian</firstname><surname>Sayers</surname><order>164</order></author><author><firstname>Lisa</firstname><surname>Capaldi</surname><order>165</order></author><author><firstname>Ashok</firstname><surname>Nikapota</surname><order>166</order></author><author><firstname>David</firstname><surname>Bloomfield</surname><order>167</order></author><author><firstname>Tim</firstname><surname>Porter</surname><order>168</order></author><author><firstname>Joji</firstname><surname>Joseph</surname><order>169</order></author><author><firstname>Cyrill</firstname><surname>Rentsch</surname><order>170</order></author><author><firstname>Ricardo 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spelling v2 66427 2024-05-15 Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol fdab5e9e2fe06c93d3ffa19c816bdcf6 John Wagstaff John Wagstaff true false 2024-05-15 MEDS BackgroundAbiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.MethodsWe analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).FindingsBetween Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial).InterpretationEnzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Journal Article The Lancet Oncology 24 5 443 456 Elsevier BV 1470-2045 2 5 2023 2023-05-02 10.1016/s1470-2045(23)00148-1 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas. 2024-06-19T15:22:56.7465510 2024-05-15T08:58:13.7814657 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Gerhardt Attard 1 Laura Murphy 2 Noel W Clarke 3 Ashwin Sachdeva 4 Craig Jones 5 Alex Hoyle 6 William Cross 7 Robert J Jones 8 Christopher C Parker 9 Silke Gillessen 10 Adrian Cook 11 Chris Brawley 12 Clare Gilson 13 Hannah Rush 14 Hoda Abdel-Aty 15 Claire L Amos 16 Claire Murphy 17 Simon Chowdhury 18 Zafar Malik 19 J Martin Russell 20 Nazia Parkar 21 Cheryl Pugh 22 Carlos Diaz-Montana 23 Carmel Pezaro 24 Warren Grant 25 Helen Saxby 26 Ian Pedley 27 Joe M O'Sullivan 28 Alison Birtle 29 Joanna Gale 30 Narayanan Srihari 31 Carys Thomas 32 Jacob Tanguay 33 John Wagstaff 34 Prantik Das 35 Emma Gray 36 Mymoona Alzouebi 37 Omi Parikh 38 Angus Robinson 39 Amir H Montazeri 40 James Wylie 41 Anjali Zarkar 42 Richard Cathomas 43 Michael D Brown 44 Yatin Jain 45 David P Dearnaley 46 Malcolm D Mason 47 Duncan Gilbert 48 Ruth E Langley 49 Robin Millman 50 David Matheson 51 Matthew R Sydes 52 Louise C Brown 53 Mahesh K B Parmar 54 Nicholas D James 55 Elin Jones 56 Katherine Hyde 57 Hilary Glen 58 Sarah Needleman 59 Ursula McGovern 60 Denise Sheehan 61 Sangeeta Paisey 62 Richard Shaffer 63 Mark Beresford 64 Zafar Malik 65 Anjali Zarkar 66 Emilio Porfiri 67 David Fackrell 68 Ling Lee 69 Thiagarajan Sreenivasan 70 Sue Brock 71 Simon Brown 72 Amit Bahl 73 Mike Smith-Howell 74 Cathryn Woodward 75 Mau-Don Phan 76 Danish Mazhar 77 Krishna Narahari 78 Jacob Tanguay 79 Fiona Douglas 80 Anil Kumar 81 Abdel Hamid 82 Azman Ibrahim 83 Dakshinamoorthy Muthukumar 84 Matthew Simms 85 Jane Worlding 86 Anna Tran 87 Mohammed Kagzi 88 Prantik Das 89 Carmel Pezaro 90 Virgil Sivoglo 91 Benjamin Masters 92 Pek Keng-Koh 93 Caroline Manetta 94 Duncan McLaren 95 Nishi Gupta 96 Denise Sheehan 97 Stergios Boussios 98 Henry Taylor 99 John Graham 100 Carla Perna 101 Lucinda Melcher 102 Warren Grant 103 Katherine Hyde 104 Ami Sabharwal 105 Uschi Hofmann 106 Robert Dealey 107 Neil McPhail 108 Robert Brierly 109 Simon Brown 110 Lisa Capaldi 111 Norma Sidek 112 Peter Whelan 113 Thiagarajan Sreenivasan 114 Peter Robson 115 Alison Falconer 116 Sarah Rudman 117 Sindu Vivekanandan 118 Vinod Mullessey 119 Sarah Needleman 120 Maria Vilarino-Varela 121 Vincent Khoo 122 Karen Tipples 123 Mehran Afshar 124 Alison Falconer 125 Patryk Brulinski 126 Vijay Sangar 127 Clive Peedell 128 Ashraf Azzabi 129 Peter Hoskin 130 Viwod Mullassery 131 Santhanam Sundar 132 Yakhub Khan 133 Ruth Conroy 134 Andrew Protheroe 135 Judith Carser 136 Paul Rogers 137 Lisa Capaldi 138 Kathryn Tarver 139 Stephanie Gibbs 140 Mohammad Muneeb Khan 141 Mohan Hingorani 142 Ashraf Azzabi 143 Simon Crabb 144 Manal Alameddine 145 Neeraj Bhalla 146 Caroline Manetta 147 Robert Hughes 148 John Logue 149 Darren Leaning 150 Salil Vengalil 151 Ashraf Azzabi 152 Daniel Ford 153 Georgina Walker 154 Ahmed Shaheen 155 Omar Khan 156 Andrew Chan 157 Imtiaz Ahmed 158 Serena Hilman 159 Fiona Douglas 160 Anil Kumar 161 Anna Tran 162 Sangeeta Paisey 163 Ian Sayers 164 Lisa Capaldi 165 Ashok Nikapota 166 David Bloomfield 167 Tim Porter 168 Joji Joseph 169 Cyrill Rentsch 170 Ricardo Pereira Mestre 171 Enrico Roggero 172 Jörg Beyer 173 Markus Borner 174 Raeto Strebel 175 Dominik Berthold 176 Daniel Engeler 177 Hubert John 178 Razvan Popescu 179 Donat Durr 180 John Wagstaff 181 66427__30375__4259e1fc9cf84066afb8e4a63387b140.pdf 66427.pdf 2024-05-15T09:00:09.7716957 Output 1145098 application/pdf Version of Record true This is an Open Access article under the CC BY 4.0 license. true eng https://creativecommons.org/licenses/by/4.0/
title Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
spellingShingle Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
John Wagstaff
title_short Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
title_full Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
title_fullStr Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
title_full_unstemmed Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
title_sort Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol
author_id_str_mv fdab5e9e2fe06c93d3ffa19c816bdcf6
author_id_fullname_str_mv fdab5e9e2fe06c93d3ffa19c816bdcf6_***_John Wagstaff
author John Wagstaff
author2 Gerhardt Attard
Laura Murphy
Noel W Clarke
Ashwin Sachdeva
Craig Jones
Alex Hoyle
William Cross
Robert J Jones
Christopher C Parker
Silke Gillessen
Adrian Cook
Chris Brawley
Clare Gilson
Hannah Rush
Hoda Abdel-Aty
Claire L Amos
Claire Murphy
Simon Chowdhury
Zafar Malik
J Martin Russell
Nazia Parkar
Cheryl Pugh
Carlos Diaz-Montana
Carmel Pezaro
Warren Grant
Helen Saxby
Ian Pedley
Joe M O'Sullivan
Alison Birtle
Joanna Gale
Narayanan Srihari
Carys Thomas
Jacob Tanguay
John Wagstaff
Prantik Das
Emma Gray
Mymoona Alzouebi
Omi Parikh
Angus Robinson
Amir H Montazeri
James Wylie
Anjali Zarkar
Richard Cathomas
Michael D Brown
Yatin Jain
David P Dearnaley
Malcolm D Mason
Duncan Gilbert
Ruth E Langley
Robin Millman
David Matheson
Matthew R Sydes
Louise C Brown
Mahesh K B Parmar
Nicholas D James
Elin Jones
Katherine Hyde
Hilary Glen
Sarah Needleman
Ursula McGovern
Denise Sheehan
Sangeeta Paisey
Richard Shaffer
Mark Beresford
Zafar Malik
Anjali Zarkar
Emilio Porfiri
David Fackrell
Ling Lee
Thiagarajan Sreenivasan
Sue Brock
Simon Brown
Amit Bahl
Mike Smith-Howell
Cathryn Woodward
Mau-Don Phan
Danish Mazhar
Krishna Narahari
Jacob Tanguay
Fiona Douglas
Anil Kumar
Abdel Hamid
Azman Ibrahim
Dakshinamoorthy Muthukumar
Matthew Simms
Jane Worlding
Anna Tran
Mohammed Kagzi
Prantik Das
Carmel Pezaro
Virgil Sivoglo
Benjamin Masters
Pek Keng-Koh
Caroline Manetta
Duncan McLaren
Nishi Gupta
Denise Sheehan
Stergios Boussios
Henry Taylor
John Graham
Carla Perna
Lucinda Melcher
Warren Grant
Katherine Hyde
Ami Sabharwal
Uschi Hofmann
Robert Dealey
Neil McPhail
Robert Brierly
Simon Brown
Lisa Capaldi
Norma Sidek
Peter Whelan
Thiagarajan Sreenivasan
Peter Robson
Alison Falconer
Sarah Rudman
Sindu Vivekanandan
Vinod Mullessey
Sarah Needleman
Maria Vilarino-Varela
Vincent Khoo
Karen Tipples
Mehran Afshar
Alison Falconer
Patryk Brulinski
Vijay Sangar
Clive Peedell
Ashraf Azzabi
Peter Hoskin
Viwod Mullassery
Santhanam Sundar
Yakhub Khan
Ruth Conroy
Andrew Protheroe
Judith Carser
Paul Rogers
Lisa Capaldi
Kathryn Tarver
Stephanie Gibbs
Mohammad Muneeb Khan
Mohan Hingorani
Ashraf Azzabi
Simon Crabb
Manal Alameddine
Neeraj Bhalla
Caroline Manetta
Robert Hughes
John Logue
Darren Leaning
Salil Vengalil
Ashraf Azzabi
Daniel Ford
Georgina Walker
Ahmed Shaheen
Omar Khan
Andrew Chan
Imtiaz Ahmed
Serena Hilman
Fiona Douglas
Anil Kumar
Anna Tran
Sangeeta Paisey
Ian Sayers
Lisa Capaldi
Ashok Nikapota
David Bloomfield
Tim Porter
Joji Joseph
Cyrill Rentsch
Ricardo Pereira Mestre
Enrico Roggero
Jörg Beyer
Markus Borner
Raeto Strebel
Dominik Berthold
Daniel Engeler
Hubert John
Razvan Popescu
Donat Durr
John Wagstaff
format Journal article
container_title The Lancet Oncology
container_volume 24
container_issue 5
container_start_page 443
publishDate 2023
institution Swansea University
issn 1470-2045
doi_str_mv 10.1016/s1470-2045(23)00148-1
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 1
active_str 0
description BackgroundAbiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.MethodsWe analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).FindingsBetween Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial).InterpretationEnzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.
published_date 2023-05-02T15:22:56Z
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score 11.012678

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